Wagner K U, Wall R J, St-Onge L, Gruss P, Wynshaw-Boris A, Garrett L, Li M, Furth P A, Hennighausen L
Laboratory of Metabolism and Biochemistry, National Institute of Diabetes Digestive and Kidney Diseases and Laboratory of Genetic Disease Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA,
Nucleic Acids Res. 1997 Nov 1;25(21):4323-30. doi: 10.1093/nar/25.21.4323.
To delete genes specifically from mammary tissue using the Cre-lox system, we have established transgenic mice expressing Cre recombinase under control of the WAP gene promoter and the MMTV LTR. Cre activity in these mice was evaluated by three criteria. First, the tissue distribution of Cre mRNA was analyzed. Second, an adenovirus carrying a reporter gene was used to determine expression at the level of single cells. Third, tissue specificity of Cre activity was determined in a mouse strain carrying a reporter gene. In adult MMTV-Cre mice expression of the transgene was confined to striated ductal cells of the salivary gland and mammary epithelial cells in virgin and lactating mice. Expression of WAP-Cre was only detected in alveolar epithelial cells of mammary tissue during lactation. Analysis of transgenic mice carrying both the MMTV-Cre and the reporter transgenes revealed recombination in every tissue. In contrast, recombination mediated by Cre under control of the WAP gene promoter was largely restricted to the mammary gland but occasionally observed in the brain. These results show that transgenic mice with WAP-Cre but not MMTV-Cre can be used as a powerful tool to study gene function in development and tumorigenesis in the mammary gland.
为了利用Cre-lox系统特异性地从乳腺组织中删除基因，我们构建了在WAP基因启动子和MMTV LTR控制下表达Cre重组酶的转基因小鼠。通过三个标准评估了这些小鼠中Cre的活性。首先，分析了Cre mRNA的组织分布。其次，使用携带报告基因的腺病毒来确定单细胞水平的表达。第三，在携带报告基因的小鼠品系中确定Cre活性的组织特异性。在成年MMTV-Cre小鼠中，转基因的表达局限于唾液腺的横纹导管细胞以及未生育和哺乳期小鼠的乳腺上皮细胞。仅在哺乳期乳腺组织的肺泡上皮细胞中检测到WAP-Cre的表达。对同时携带MMTV-Cre和报告转基因的转基因小鼠的分析显示，每个组织中均发生了重组。相比之下，在WAP基因启动子控制下由Cre介导的重组主要局限于乳腺，但偶尔在大脑中也可观察到。这些结果表明，具有WAP-Cre而非MMTV-Cre的转基因小鼠可作为研究乳腺发育和肿瘤发生过程中基因功能的有力工具。
